NEUROPATHOLOGY CORE ? CORE G: PROJECT SUMMARY/ABSTRACT The BIOCARD study is a longitudinal, observational study of 349 individuals who were cognitively normal and primarily middle aged (mean age=57.1) at enrollment. The subjects have now been followed for up to 27 years. The overall objectives of the project are to further advance the study of preclinical Alzheimer?s disease by: (1) clarifying the pattern and rate of change in AD biomarkers (including those based on CSF, blood, MRI, and PET imaging) and cognition; the biomarkers to be studied include several promising novel biomarkers derived from blood, CSF and brain imaging. (2) maximizing our data by working collaboratively with several research groups who have comparable data, and (3) providing a publicly accessible data, brain scans, and biological specimens, for researchers in the field. To accomplish these goals we established 7 Cores and, with this application, are also including 2 projects. The Neuropathology Core (Core G) is responsible for overseeing the neuropathological assessment of brain tissue from participants in the BIOCARD study and for assuring the integration of these findings with relevant data collected by the other Cores and Projects. The specific aims include: (1) to maintain a registry of prospective brain donors, (2) to arrange and perform neuropathologic autopsies, (3) to provide neuropathologic diagnoses, (4) to integrate neuropathology data with data from other Cores and Projects, (5), to prepare, store and distribute autopsy brain tissue for research, and (6) to continue investigations of the early pathogenesis of Alzheimer?s disease.